Project Title

The long-term consequences of pulmonary tuberculosis and respiratory viruses on lung health in young South African children

EDCTP Project Call

Senior Fellowship Plus (SFP)

Project Objectives

The overarching goal of the TB-lung FACT2 project is to improve our current understanding of the long-term impact of PTB and other LRTIs on lung health in children living in resource-limited settings.

Study Design

Prospective observational cohort study

Project Summary

The TB-lung FACT2 project aims to investigate the long-term impact of PTB and common viral LRTIs on lung health in young children across representative and well-characterised disease categories and spectrum in order to reduce respiratory morbidlity and mortality. We propose to use the well-established, previously EDCTP supported and unique TB-lung FACT cohort of 300 well-characterized HIV-infected and uninfected children aged 0-13 years (median age 2 years), systematically investigated for M. tuberculosis and other respiratory pathogens. This cohort is complemented by 100 healthy controls to support the rigorous investigation of the long-term lung health impact of TB and LRTI in children. Through this proposed research, we will extend the current 6 months follow-up of the existing TB-lung FACT cohort for an additional 30 months (36 months total) to measure lung function longitudinally, using state of the-art rigorous lung function testing including oscillometry, plethysmography and diffusion capacity. For analytical purposes, children will be classified into three groups: 1) TB cases, 2) children in whom TB is excluded after investigation (“ill controls”), and 3) age-matched healthy controls. The INHALE study aims to investigate the impact of PTB and viral LRTIs on lung health in young Mozambican children. The study will leverage a cohort of children with presumptive PTB enrolled in the Stool4TB project (EDCTP funded), which aims to recruit HIV infected and uninfected children under 8 years of age by adding lung health assessment, including the sampling for respiratory virus infections and extend follow-up for intermediate lung health outcomes. The project will build capacity for clinical pediatric lung health research in rural Mozambique, within the context of a well-established African research center with an extensive track record for research on TB and infectious diseases (The Centro de Investigação em Saúde de Manhiça / Fundação Manhiça (CISM/ FM).

Host Organisation

Sites

Project Title

The impact of pulmonary tuberculosis and other lower respiratory tract pathogens on lung function in young South African children

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

To investigate the effect of TB, TB/ HIV co-infection and other common respiratory pathogens on lung function in young children.

Study Design

Prospective observational cohort study of children with suspected pulmonary TB including healthy controls

Project Summary

This EDCTP funded project called TB- lung FACT or Umoya study (“breath” in isiXhosa) is a hospital-based study that rigorously and systematically investigates the lung health of a cohort of 300 HIV-infected and uninfected children 0-13 years of age, with different spectrum of intrathoracic (pulmonary) tuberculosis (TB). Participants are recruited consecutively from children routinely presenting to 2 regional hospitals requiring routine investigation as suspected TB cases. At enrollment, two respiratory samples (any of gastric aspirate [children unable to expectorate], expectorated sputum [older children], induced sputum) from children with suspected intrathoracic TB will be analyzed by smear, culture and GeneXpert Ultra. Minimally invasive samples (blood, urine and stool) will be collected for biomarker work and for storage for future use. In addition, respiratory pathogens and the respiratory microbiome will be tested on nasopharyngeal aspirates collected at baseline and follow-up. Lung function is measured using the novel non-invasive Whistler technique at baseline and at follow- up over 6 months, to track changes in lung function and evaluate functional outcomes. All children undergo clinical and radiological follow-up. The sample size of 300 children with suspected TB will be complemented by 50 healthy sibling controls for the respiratory microbiome and lung function and lung health evaluation (total study population n=350). This study has the aim to investigate the effect of TB, TB/ HIV co-infection and other common respiratory pathogens on lung function in young children. It will investigate the effect of respiratory diseases like TB and respiratory viruses on lung function in young children. In addition it will investigate the changes in lung function measurements over time in these children. The study was approved by the local health research ethics committee from Stellenbosch University and started 23-November-2017. At the end of June 2019; 201 children were enrolled, of which 75 cases, 89 ill controls, healthy sibling controls, and 4 children withdrew. Of the cases 34/75 (45%) were microbiologically confirmed TB. Nasopharyngeal aspirates for viruses and the respiratory microbiome was collected in 195/201 children. Whistler lung function was successful in 83/201 children, with repeat measurements in 25 children. In addition, a total of 107 Spirometry measurements were done (children >4 years of age), with 35 repeat measurements. The impact of this research project will be to help better understand the effect of TB and other pathogens in children living in a resource-limited setting. There is an increasing call for more research into the long-term Reference: 99726 TB- Lung FACT TMA 2015 CDF – 1012 Date submitted: 30-Augustus-2019 Page 9 of 45 Generic Periodic Reporting Template v1 consequences of TB lung disease. The aims of this study are very timous and will allow us to built a cohort of children that can be followed up long-term to investigate effects of TB disease on long-term lung health. The knowledge gained would enable interventions to be implemented to potentially limit disabling chronic lung disease in children and adults, especially COPD. A sound evidence base for the utility of lung function assessment in the study population may also considerably impact on routine clinical care through more objective and feasible assessment of lung function in young children. The principal investigator (Dr Marieke vd Zalm) has has co-organized the first international post TB symposium in 22-23 July 2019, in Stellenbosch. https://blogs.sun.ac.za/dttc/about-us/our-funders-and-research-partners/

Host Organisation

Sites

Results & Outcomes

Current Organisation

Stellenbosch University, Desmond Tutu TB Centre

Current Job Title

Paediatrician and Clinical researcher

Biography